EDITORIAL
Journal of Cachexia, Sarcopenia and Muscle (2017)
Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/jcsm.12192
Anorexia of ageing: a key component in the
pathogenesis of both sarcopenia and cachexia
John E. Morley*
Division of Geriatric Medicine, Saint Louis University School of Medicine, 1402 S. Grand Blvd., M238, St. Louis, MO, 63104, USA
Abstract
The anorexia of aging was first recognized as a physiological syndrome 30 years ago. Its major causes are an alteration in
fundal compliance with an increase in antral stretch and enhanced cholecystokinin activity leading to increased satiation.
This anorexia leads to weight loss in aging persons and is one of the component causes of the aging related sarcopenia.
This physiological anorexia also increases the risk of more severe anorexia when an older person has an increase in
inflammatory cytokines such as occurs when they have an illness. This results in an increase in the anorexia due to
cachexia in older persons.
Keywords
Anorexia; Aging; Cachexia; Sarcopenia
Anorexia is an important component of the cachexia syndrome1,2 and also plays a role in the pathogenesis of
sarcopenia.3–5 In a community study, anorexia was shown
to be independently associated with sarcopenia.6 With ageing, there is a decrease in food intake known as the anorexia
of ageing coupled with a decline in muscle mass and an
increase in fat mass.7–9 The protective effect of obesity, especially when an older person becomes ill, is well recognized—
the obesity paradox.10–13
The physiological anorexia of ageing places the older
person at increased risk of severe anorexia and weight
loss when they develop an illness associated with an
increased in inflammatory cytokines or an increase in tumours producing lactate.14–17 There are multiple causes
of the anorexia of ageing (Figure 1).18–20 Declining smell
and taste plays a minor role in the decreased food intake.
Changes in compliance of the fundus of the stomach due
to nitric oxide deficiency and decreased antral stretch play
a major role in postprandial anorexia, as does delayed gastric emptying in response to large meals.21–23 Because of
this, there is an increase in food intake when liquid dietary
supplements are used rather than solid food.24 Cholecystokinin (CCK) is the major gastrointestinal satiety hormone.25
CCK levels increase with ageing, and CCK is a more effective satiety agent with ageing.26,27 Other gut satiety
hormones
like
gastrin-releasing
peptide/bombesin,
glucagon-like peptide 1 and amylin do not appear to
change much with ageing.28,29 Leptin, a hormone produced
by adipose cells, increases with increased fat mass and appears to play a role in the anorexia of ageing.30,31 Hypertriglyceridemia blocks the ability of leptin to cross the blood–brain
barrier.32 Male hypogonadism leads to an increase in leptin.33
The effects of ageing on ghrelin are controversial.34 The
ghrelin analogue, anamorelin, is a potent enhancer of food
intake.35,36
The central regulation of feeding is a very complicated
process.37 Multiple monoamines (especially serotonin and
norepinephrine) and neuropeptides (e.g. neuropeptide Y,
melanocortin, corticotrophin-releasing factor) converge on
the nitric oxide/methylmalnyl coenzyme A system to modulate food intake.16,37–40 Serotonin is a particularly anorectic agent, and in cancer, the effect of serotonin is
© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the
original work is properly cited.
2
Editorial
Figure 1 Simplified diagram of factors involved in the pathogenesis of the anorexia of ageing. CRF, corticotrophin releasing hormone; NPY, neuropeptide Y; MSH, melanocyte-stimulating hormone; CCK, cholecystokinin.
potentiated.41 Ghrelin produces its effects by stimulating
nitric oxide synthase.42 The ghrelin agonist, GHRP-2, has
been shown to increase food intake in persons with
anorexia nervosa.43 Lactate, which is elevated in many
cancers, has a direct inhibitory effect on methylmalonyl
coenzyme A.16
Sarcopenia is defined as the decline in function due to the
loss of muscle mass.44,45 There are multiple causes of
sarcopenia.46 The age-related anorexia decreases muscle
mass, and this can be aggravated by low grade production
of inflammatory cytokines in chronic disease.6,47
Persons with the anorexia of ageing are at risk of
developing severe anorexia when exposed to high levels
of inflammatory cytokines as occurs in the anorexia–
cachexia syndrome.48–50 Persons with illnesses are apt to
develop depression with an increase in the anorectic
neurotransmitters, serotonin and corticotrophin-releasing
factor.37,38
The data presented here support the concept that the
anorexia of ageing is a major risk factor for older persons
developing sarcopenia and/or cachexia. In addition, weight
loss together with sarcopenia are major causes of the
physical frailty syndrome.51–54 For these reasons, we
strongly recommend regularly monitoring and treating nutritional abnormalities in older persons.55–58 When anorexia
is associated with weight loss, the appropriate nutritional
supplement is a leucine-enriched essential amino acid
mixture.59,60 Drugs such as dronabinol and megestrol acetate have a small effect in increasing food intake.61,62 Other
drugs are under development to increase food intake
and/or decrease muscle wasting.63
Acknowledgements
The authors certify that they comply with the ethical guidelines for authorship and publishing of the Journal of Cachexia,
Sarcopenia and Muscle.64
Conflicts of Interest
The author has no conflict of interest regarding this work.
Journal of Cachexia, Sarcopenia and Muscle 2017
DOI: 10.1002/jcsm.12192
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Editorial
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